Various porphyrins are being studied in an attempt to understand why some of them show a relatively high accumulation and/or retention in malignant tissue. Using autoradiographic and fluorescent methods, we find that hematoporphyrin derivative (Hpd) accumulates in the mouse in the following order: liver-kidney-spleen-lung-tumor (SMT-F)-skin-muscle. However, the intratissue distribution changes with time after injection in all tissues except the tumor which maintains a 5 to 1 preference for porphyrin retention in the stroma for at least 72 hours. Normal tissues clear Hpd as plasma levels drop (half-life equals 3 hours). However, even in normal tissues, stromal preference is apparent at clearance since these areas clear more slowly. Hematoporphyrin (HP), however, shows no tendency for intracellular accumulation in any tissues, normal or malignant, but is retained mainly in the stroma. Its clearance from tissue is more rapid than that of HpD.